1. Field of the Invention
The present invention relates to a scanning probe microscope suitable for observing a sample of a long body elongated to be long on a board, particularly relates to a scanning probe microscope (SPM) technology capable of reading information of a single piece of DNA without modification.
2. Description of Related Art
In present age, DNA arrangement analysis becomes a technology which is extremely important in biological researches and medical diagnoses. DNA forms two pieces of chains in a spiral shape based on base pairs of A-T, G-C, and when heated, two pieces of chains are disentangled to constitute one piece chain. The basis of DNA arrangement analysis is constituted by retaining a state of the single piece of chain by rapidly cooling the single piece chain DNA and successively reading information inscribed to the single piece chain DNA.
Further, it is known that when the single piece chain DNA which has been constituted by being heated is gradually cooled, an original pair of the single piece chains DNA is combined to recover to the two pieces chain DNA. The phenomenon is referred to as hybridization and the term is used also for the phenomenon in which ribonucleic acid (RNA) having gene information is combined with a single piece of chain DNA at pairing arrangement positions. Medical or biological diagnoses are carried out by inspecting whether RNA to which attention is paid differs in a standard position with regard to DNA a standard arrangement of which has already been known.
Now, although in such analysis, it is requested to read DNA information from an end thereof, at present, there has not been developed a technology of forming a sample in a state in which a single piece of long DNA is elongated from end to end and successively reading information inscribed thereto from the end. In a DNA sequencer of the related art, information of single piece chain DNA is provided by an enormously troublesome operation of cutting two pieces of chains of DNA constituting a chromosome to a specific length hierarchically by using a restriction enzyme, modifying a fluorescent substance at an end thereof, reading information of individual cut DNA, ascribing DNA which has been continuous in an original single piece chain from information of the end portion, and resynthesizing hierarchical cutting. Although the operation has been carried out by a large-scaled computer, enormous time is taken and further, resynthesis is frequently failed.
Under such a situation, Patent Reference 1 has been provided with an object of providing a gene arrangement reading apparatus capable of directly reading respective code arrangement of four bases of A (adenine), C (cytosine) , G (guanine), or U (uracil) or T (thymine) of a single piece chain of RNA or DNA. According to the technology, in order to detect a specific one base of A, C, G or U or T, by bonding a base having gene information to a tip portion of a metal stylus via an adhesive binder of nanometer order having a strong bonding affinity with an organic function group such as a carbon nanotube at the tip portion of the metal stylus of a scanning probe microscope (SPM), an attraction force produced by a hydrogen bond utilizing complimentarity particular to the base is detected.
Although Patent Reference 1 explains that base arrangement information can be read by the above-described constitution with regard to the hierarchically cut DNA, an explanation has not been given of how riobonucleic acid constituting a sample is linearly fixed onto a board such that the stylus (hereinafter, described as probe for simplification) of the scanning microscope can trace, further, of a method of firmly tracking the elongated single piece chain of RNA or DNA by a probe.
The inventors have started to develop a general apparatus of detecting a number of kinds of information with regard to an elongated single piece DNA in view of establishing a prospect of a pretreatment technology of a sample in which long DNA is fixed in a state of being elongated in one direction by a method of constituting a single piece chain DNA which is normally in a state of two pieces of chains in an aqueous solution, hybridizing the single piece DNA by known RNA, DNA or polypeptide nucleic acid (PNA), labeling by fluorescence or metal colloid, and thereafter temporarily sinking and pulling up a board by traversing a gas/liquid interface of the aqueous solution of DNA.
[Patent Reference 1] JP-A-2002-350435 “Apparatus of reading gene arrangement”, publication date: Dec. 4, 2002